For over 15 years our research team and others have taken Kanner's original observations about personality features characteristic of some parents of autistic individuals and developed definitions of, and standardized measures for, a broader autism phenotype. The broad autism phenotype (BAP) is thought to represent the phenotypic expression of the genetic liability to autism in non-autistic relatives of autistic probands, and is defined by characteristics that are milder but qualitatively similar to the defining features of autism. This work has potential importance for 1) teasing apart the gene-behavior relationships in autism, 2) understanding brain-behavior relationships in autism and, 3) providing additional qualitative and quantitative information on the range and nature of the phenotypic expression of autism genes, which may augment our ability to find those genes. While autism and the BAP are defined by particular behavioral characteristics, they are clinically and etiologically heterogeneous, and are the end result of a range of underlying neuropsychological, neural and genetic mechanisms. In this project we propose to examine the relatives of autistic and Down syndrome probands on selected neuropsychological measures of social cognition, central coherence and executive function, three principal cognitive frameworks proposed as theories to explain the neuropsychological basis of autism. These neuropsychological characteristics will be examined in relationship to our clinically-based measures of the BAP, in order to both elucidate the neuropsychological basis of the BAP and to provide efficient, valid and reliable measures for future studies of the BAP. Autism and OS relatives will be compared in these three neuropsychological domains, to a unique sample of individuals with focal brain lesions in the amygdala, orbital-frontal cortex and right somatosensory cortex, drawn from a brain injury registry at the University of Iowa, to provide insights into the neural basis of the behavioral and neuropsychological characteristics of autism and the BAP. Finally, patterns of co-occurrence of these characteristics will be examined in individuals and families. This study will complement ongoing studies of the same neuropsychological characteristics in autistic probands. This project brings together a unique group of experienced researchers with complementary expertise in family-genetic (Piven) and neuropsychological studies of autism (Happ[unreadable]), and in the neural basis of social cognition (Adolphs), to study the neuropsychological basis of the broad autism phenotype.